Is Erectile Dysfunction Associated With a Higher Risk of Cardiovascular Disease?

Authors:
Eric A. Dietrich, PharmD, BCPS, and Kyle Davis, PharmD, BCPS

Citation:
Dietrich EA. Is erectile dysfunction associated with a higher risk of cardiovascular disease? Consultant. 2018;58(7):185-186.

JB is a 62-year-old man with a history of hypertension and obesity. He presents for his annual routine physical examination. His blood pressure is 128/72 mm Hg and has been very well controlled on amlodipine, 5 mg daily. He weighs 97.5 kg, and his weight has decreased 2 kg over the past year as a result of diet and exercise.

Results of laboratory blood tests include a total cholesterol level of 175 mg/dL, a high-density lipoprotein (HDL) level of 35 mg/dL, a triglyceride level of 150 mg/dL, and a calculated low-density lipoprotein (LDL) level of 80 mg/dL; all other results are within normal limits. JB’s estimated 10-year risk of atherosclerotic cardiovascular disease (ASCVD) events is calculated at 9%.

In the past, you have discussed the risk of ASCVD events with JB, but given his marginal risk, age, very well-controlled blood pressure, and overall health, he has declined statin therapy, because he feels that he has little to gain but more to lose in regard to the medication’s costs and adverse effects.

Today, JB reports recent problems with erectile dysfunction (ED) and is seeking treatment for his symptoms, which have been determined to be of vascular origin. Does the presence of ED change his perceived risk of CVD events?

NEXT: The Evidence

The Evidence

Several underlying mechanisms of ED exist, including hormonal, neurological, psychogenic, and vascular etiologies. The pathophysiology of ED due to vascular causes shares many characteristics with ASCVD: endothelial dysfunction, atherosclerosis, and inflammation. Furthermore, many risk factors for vascular ED are also risk factors for ASCVD, such as obesity, diabetes, smoking, and hypertension. Given this overlap, it stands to reason that vascular ED may be associated with an increased risk of ASCVD events, yet this relationship has not been widely recognized and is not included as a risk factor for CVD in major societal guidelines.

In 2010, Böhm and colleagues published an analysis of 2 hypertension studies, ONTARGET and TRANSCEND, in which they performed a subanalysis on patients with or without ED at baseline to determine the incidence of ASCVD events throughout the study period.¹ Over both studies, the presence of ED at baseline among the 1922 total participants was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.84; 95% CI, 1.21-2.81) as well as the composite of ASCVD-related death, myocardial infarction, hospitalization for heart failure, and stroke (HR, 1.42; 95% CI, 1.04-1.94). Interestingly, study treatments did not modify the risk of CVD events.¹

A more recent analysis conducted by Uddin and colleagues utilized the Multi-Ethnic Study of Atherosclerosis cohort to determine the association between ED and CVD events.² A total of 1914 participants were included in the analysis, with 45.8% (877) reporting ED symptoms; the average follow-up period was 3.8 years. Three models were generated, adding additional controlling factors such as baseline comorbidities, medication use, and depression. In the unadjusted analysis, the presence of ED was associated with a significant increase in the risk of ASCVD events (HR, 2.6; 95% CI, 1.6-4.1); in the fully adjusted model, ED remained a significant risk factor for ASCVD events (HR, 1.9; 95% CI, 1.1-3.4), but the risk of coronary artery disease events was no longer statistically significant.²

NEXT: Clinical Application

Clinical Application

Vascular ED, caused by microvascular damage to the arteries of the penis, carries a high risk of ASCVD events. It seems logical that microvascular damage to the penis leading to ED would not be exclusively confined to arteries of the penis; the mechanisms by which that damage was caused (eg, smoking, obesity, hypertension, diabetes) would lead to arterial damage in other organs such as the heart and the brain. The analyses by Böhm and colleagues and Uddin and colleagues confirm this suspicion by showing a nearly 2-fold increase in the risk of ASCVD events in men with ED.

Because both of these analyses were observational, a true causative relationship cannot be definitively determined, but given the similar underlying pathophysiology of the 2 disease states, it is unlikely that the observed relationship is due to chance alone. However, due to this limitation, it appears less likely that ED will be recognized as a formal ASCVD risk factor, and it is unclear whether CVD risk reduction therapies will reduce the risk for ASCVD events in patients with ED.

In patients with a high estimated risk of ASCVD events, statin therapy, along with other treatment modalities such as smoking cessation, blood pressure control, weight reduction, and antiplatelet agents, is clearly indicated. In patients with equivocal indications for statin therapy, other potentially influencing factors must be considered in order to help elucidate the risk-to-benefit ratio on a per patient basis.

In the case of JB, his estimated 10-year risk for ASCVD events is 9%, but given his age and overall health, withholding statin therapy may be warranted if this is his preference. However, with his development of ED symptoms, it seems that his estimated ASCVD risk may be falsely low in light of the results of the studies discussed above. While it is unclear exactly whether the benefits of statin therapy in reducing the risk of ASCVD events would be increased now that JB has developed ED symptoms, it seems reasonable to try to maximize his ASCVD risk-lowering therapies, since the presence of ED may increase his risk for ASCVD events 2-fold and is not accurately captured in his current risk estimation.

NEXT: Outcome of the Case

Outcome of the Case

The results of the studies showing a nearly 2-fold increase in the rate of ASCVD events in patients with ED should be discussed with JB, as well as the similar pathophysiologic mechanisms behind ASCVD and vascular ED. While his estimated 10-year risk is only estimated to be 9% it is likely his true risk is much higher with the development of ED symptoms.

While no data exist to definitely support a role for statin therapy in this setting, given that his current 10-year risk exceeds the recommended threshold for beginning statin therapy, this additional unmeasured risk factor of ED likely tips the scale toward beginning a statin. JB would be started on rosuvastatin, 10 mg daily, and have baseline measurements of aspartate aminotransferase and alanine aminotransferase today; any moderate-intensity statin could be started, but rosuvastatin or pravastatin would be preferred in order to minimize any potential drug-drug interactions with ED medications that might also be prescribed. 

Eric A. Dietrich, PharmD, BCPS, is a graduate of the University of Florida College of Pharmacy and completed a 2-year fellowship in family medicine where he was in charge of an anticoagulation clinic. He works for the College of Pharmacy and the College of Medicine at the University of Florida in Gainesville.

Kyle Davis, PharmD, BCPS, is a graduate of the University of Florida College of Pharmacy in Gainesville and completed a 2-year residency in internal medicine at Indiana University in Indianapolis. He is an internal medicine specialist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

References:

1. Böhm M, Baumhäkel M, Teo K, et al; ONTARGET/TRANSCEND Erectile Dysfunction Substudy Investigators. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation. 2010;121(12):1439-1446.
2. Uddin SMI, Mirbolouk M, Dardari Z, et al. Erectile dysfunction as an independent predictor of future cardiovascular events: the Multi-Ethnic Study of Atherosclerosis. Circulation. 2010;121(12):1439-1446.